A phase 2 clinical trial testing DPX-Survivac and metronomic low dose cyclophosphamide as immunotherapy for patients with recurrent diffuse large b-cell lymphoma.

e14578 Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell lymphoma (DLBCL) patients. DPX-Survivac contains survivin HLA class I peptides in a novel formulation, DepoVax. A phase 1 trial in ovarian cancer patients demonstrated the safety and immunogenicity of DPX-Survivac therapy. A phase 2 trial was initiated to determine the objective response rate, immunogenicity and safety in patients with recurrent, survivin-expressing DLBCL who are not eligible for transplant, or who have recurred after transplant. Methods: 24 subjects with confirmed survivin-positive DLBCL with LDH's less than 2x normal, are to be enrolled in this study. Patients receive two 0.25 mL priming doses of DPX-Survivac three weeks apart and up to six 0.1 mL boosting doses eight weeks apart in combination with low dose oral metronomic cyclophosphamide. Subjects will be treated for one year or until disease progression. The objective response rate is measured using Modified Cheson criteria. Biopsy and blood specimens will be collected for correlative biomarker and immune analyses. Safety will be documented by CTCAE v4.03 Results: Four subjects to date have been screened or enrolled in this trial, and two have completed priming and at least one boosting vaccination. The treatment was well tolerated. Both of these two subjects had progressive disease on study day 100 and 162, before completing treatment. One demonstrated a robust systemic antigen-specific T cell response. The subject that did not demonstrate immune responses post- vaccination had low peripheral blood lymphocyte counts at study entry. For the subject with a systemic immune response, it correlated with increased T cell infiltrates in the tumor tissue. Tumor biopsy analysis revealed that both patients had expression of PD-1 and PD-L1 within the tumor tissue. Conclusions: Early results suggest that this immunotherapy approach is feasible with patients with recurrent DLBCL. The interim analysis of the current study provides clinical and biological rationale for combining the vaccine/cyclophosphamide therapy with other cancer immunotherapeutic strategies, such as checkpoint modulators. Clinical trial information: NCT02323230.